Immunohistochemical characterization of type II pneumocyte proliferation after challenge with type I porcine reproductive and respiratory syndrome virus.

The aim of this study was to characterize histologically and immunohistochemically the lung lesions developing in growing pigs, 10 and 21 days after experimental challenge with a field strain of porcine reproductive and respiratory syndrome virus (PRRSV). Lung lesions were scored for (1) pneumocyte hypertrophy and hyperplasia, (2) septal mononuclear infiltration, (3) intra-alveolar necrotic debris, (4) intra-alveolar inflammatory cell accumulation and (5) perivascular inflammatory cell accumulation. Immunohistochemistry was performed using antibodies specific for cytokeratin, Ki67, thyroid transcription factor (TTF)-1, the myelomonocytic marker MAC387 and PRRSV. Anti-TTF-1 identified type II pneumocytes and there was marked proliferation of these cells compared with control lung (P <0.05). Anti-cytokeratin labelled type I and II pneumocytes as well as bronchial epithelial cells; however, this labelling was not suitable for cell counting purposes. There was a correlation between lesion severity and the number of cells expressing Ki67 (P <0.05).

Efficacy of protected sodium butyrate, a protected blend of essential oils, their combination, and Bacillus amyloliquefaciens spore suspension against artificially induced necrotic enteritis in broilers.

Necrotic enteritis caused by Clostridium perfringens leads to serious economical losses to the poultry industry. There is a growing need to find effective, nontoxic, antibiotic alternatives to prevent and cure the disease. In our study, the efficacy of protected sodium butyrate at 1.5 g/kg (BP70), a Bacillus amyloliquefaciens spore suspension with 10(9) cfu/g (BAL; Ecobiol), a protected blend of essential oils (1%) at 1.5 g/kg (EO), and a combination of sodium butyrate with essential oils (1%) protected with vegetable fat at 1.5 g/kg (BP70+EO; Natesse) was investigated in an artifical C. perfringens-infection model. Body weight gain, gross pathological and histopathological lesion scores, villus lengths, and villus length:crypt depth ratio was determined and compared with the control group. Broilers infected with C. perfringens and treated with essential oils or the combination of sodium butyrate and essential oils showed significantly better BW gain (P < 0.05), increased villus length and villus length:crypt depth ratio (P < 0.001), and decreased gross pathological and histopathological lesion scores (P < 0.05) compared with the control. Sodium butyrate alone and B. amyloliquefaciens spore suspension had no beneficial effects on the course of the disease in this study. According to our results, the protected combination of sodium butyrate and essential oils, as well as the protected essential oils, can be potential candidates for the prevention and treatment of necrotic enteritis in broiler chickens.

Expression of claudin-4 molecule in canine exocrine pancreatic acinar cell carcinomas.

AIMS: Claudins, integral membrane proteins are components of the tight junction structures between epithelial and endothelial cells. These transmembrane proteins create a primary barrier to prevent paracellular transport of solutes, and also restrict the lateral diffusion of membrane lipids and proteins to maintain the cellular polarity. The aim of the present study was to characterise the expression pattern of claudin-4 tight junction molecule in canine normal pancreatic tissues and in the well-differentiated and poorly-differentiated pancreatic acinar cell carcinomas in canines. METHODS AND RESULTS: The necropsy samples included canine intact pancreatic tissues, and canine well-differentiated and poorly-differentiated pancreatic acinar cell carcinomas samples. Claudin-4 was detected as an intense lateral membrane labelling of acinar cells in all intact pancreatic tissues. The intact epithelial cells of the different ducts were negative for the claudin-4 molecule. All primary and secondary canine well-differentiated exocrine pancreatic acinar cell carcinoma tissues showed intense apical lateral positivity for the claudin-4 molecule. All primary and secondary poorly-differentiated pancreatic acinar cell carcinoma tissues showed diffusely the loss of claudin-4 expression. CONCLUSION: Consequently, we hypothesize that the loss of expression of claudin-4 plays a role in the progression of canine pancreatic acinar cell carcinoma and may lead to cellular detachment, disorientation and invasion of these pancreatic cancers. Furthermore, claudin-4 can be used as an immunohistochemical marker to distinguish canine well-differentiated and undifferentiated exocrine pancreatic acinar cell carcinomas.

First occurrence of periosteal chondroma (juxtacortical chondroma) in Uromastyxmaliensis (Reptilia: Sauria: Agamidae).

The occurrence of a periosteal chondroma (juxtacortical chondroma) in an adult male Uromastyx maliensis is documented for the first time. The chondroma developed near the right shoulder joint from the periosteal membrane, causing partial atrophy in the surrounding skeletal muscles. In the chondroma tissues widespread central necrosis and secondary calcium salt deposition were observed. Monomorphic chondrocytes were irregularly spread in the chondromucin matrix. The lizard had locomotor problems due to irritation of the periosteum and reduced movement of the bones constituting the shoulder joint caused by the chondroma.

Plasma and salivary 6beta-hydroxycortisol measurements for assessing adrenocortical activity in patients with adrenocortical adenomas.

The aim of this study was to examine and compare the potential usefulness of plasma and salivary 6beta-hydroxycortisol measurements for assessing adrenocortical activity in patients with adrenocortical adenomas. Plasma and salivary cortisol as well as 6beta-hydroxycortisol determinations were performed by radioimmunoassay after extraction with ethyl acetate followed by chromatographic separation using a modified paper chromatographic system. Samples were obtained from 36 control subjects and 37 patients with non-hyperfunctioning adrenocortical adenomas in the morning at 8 a.m. after a low-dose of dexamethasone and after stimulation with synthetic depot ACTH. Basal and post-dexamethasone hormone levels were also measured in plasma and salivary samples of 4 patients with Cushing's syndrome from adrenal adenomas. In the baseline state, patients with non-hyperfunctioning adrenocortical adenomas had significantly higher plasma and salivary 6beta-hydroxycortisol levels (mean+/-SE, 79.0+/-7 and 17.1+/-2.2 ng/dl, respectively) compared to those measured in controls (62.0+/-4 and 7.7+/-0.6 ng/dl, respectively), whereas baseline plasma and salivary cortisol levels (9.6+/-0.5 microg/dl and 342+/-39 ng/dl, respectively) were similar to those measured in the control group (9.9+/-0.4 microg/dl and 366+/-24 ng/dl, respectively). In all groups, the changes in plasma and salivary 6beta-hydroxycortisol concentrations after dexamethasone suppression and ACTH stimulation were similar to the changes in plasma and salivary cortisol levels, although the differing ratios of 6betaOHF to cortisol indicated potentially important variations in the induction of 6beta-hydroxylase activity between the three groups. In patients with Cushing's syndrome, baseline plasma and salivary 6beta-hydroxycortisol concentrations (754+/-444 and 104+/-88 ng/dl, respectively) were more markedly increased than plasma and salivary cortisol levels (24.8+/-6.7 microg/dl and 1100+/-184 ng/dl, respectively), and all remained non-suppressible after dexamethasone administration. These results suggests that plasma and salivary 6beta-hydroxycortisol determinations may precisely detect not only overt increases of cortisol secretion in patients with Cushing's syndrome but also mild glucocorticoid overproduction presumably present in patients with non-hyperfunctioning adrenocortical tumors.

Leptin inhibits cortisol and corticosterone secretion in pathologic human adrenocortical cells.

Regulation of adrenal corticosteroid secretion by leptin may involve interactions at multiple levels of the hypothalamic-pituitary-adrenal axis. To investigate the possible direct effects of leptin on corticosteroid secretion of human adrenocortical adenomas, cells from adrenocortical adenomas causing primary aldosteronism (n = 1) and Cushing's syndrome (n = 1), as well as cells from nonhyperfunctioning adrenocortical adenomas (n = 5) were isolated and incubated for 2 h with human recombinant leptin (1-1000 ng/ml) in the presence and absence of adrenocorticotrop hormone (ACTH), then cortisol, corticosterone and aldosterone concentrations in incubating media were determined using radioimmunoassays. It was found that leptin effectively and dose-dependently inhibited basal and ACTH-stimulated cortisol and corticosterone secretion in the three types of human adrenocortical adenoma cells. The inhibiting effect of basal corticosterone secretion was detectable in the presence of leptin concentration as low as 1 ng/ml, with decreases of corticosterone secretion to 34+/-4%, 57+/-11% and 79+/-9% in Cushing's syndrome, primary aldosteronism, and nonhyperfunctioning adrenocortical adenoma cells, respectively. The inhibition of basal cortisol secretion in the presence of low concentration of leptin was less prominent, but 10 ng/ml leptin significantly diminished basal cortisol secretion to 81+/-9% in adrenocortical adenoma cells from Cushing's syndrome, to 68+/-6% in adenoma cells from primary aldosteronism, and to 83+/-8% in cells from nonhyperfunctioning adenomas. The inhibition of ACTH-stimulated cortisol and corticosterone secretion by leptin was similar to those found in cells without ACTH stimulation. By contrast, leptin even at 1000 ng/ml concentration exerted no clear effect on basal and ACTH-stimulated aldosterone secretion in cells from primary aldosteronism and in those nonhyperfunctioning adenoma cells in which aldosterone secretion was detectable. These results indicate that leptin is a potent inhibitor of cortisol and corticosterone secretion in human adenomatous adrenocortical cells. The inhibition of these corticosteroids by leptin may represent a potentially important interaction that exists between leptin and the hypothalamic-pituitary-adrenal axis.

Comparative analysis of plasma 17-hydroxyprogesterone and cortisol responses to ACTH in patients with various adrenal tumors before and after unilateral adrenalectomy.

Patients with non-hyperfunctioning adrenal adenomas often have an increased plasma 17-hydroxyprogesterone response to ACTH stimulation. The effects of adrenal surgery on this abnormality have rarely been investigated. One hundred and sixty-one patients with unilateral adrenal tumors (non-hyperfunctioning adenomas, 78; cortisol-producing adenomas, 8; aldosterone-producing adenomas, 37; adrenal cysts, 12; pheochromocytomas, 26) were studied. Patients before and after adrenal surgery as well as 60 healthy subjects underwent an ACTH stimulation test using 2 mg synthetic ACTH(1-24) (Cortrosyn Depot, Organon). Basal and ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations are reported. Before adrenal surgery, the basal plasma 17-hydroxyprogesterone concentrations were normal in patients with all types of tumors. However, the ACTH-stimulated plasma 17-hydroxyprogesterone levels were abnormally increased in 53% and 31% of patients with non-hyperfunctioning adenomas and aldosterone-producing adenomas, respectively. In addition, a few patients with adrenal cysts and pheochromocytomas also showed an increased ACTH-stimulated 17-hydroxyprogesterone response. After unilateral adrenalectomy, this hormonal abnormality disappeared in most, although not all patients with adrenal tumors. In patients with non-hyperfunctioning adrenal tumors, ACTH-stimulated plasma 17-hydroxyprogesterone and cortisol concentrations significantly correlated with the size of the tumors. These results firmly indicate that the tumoral mass itself may be responsible for the increased plasma 17-hydroxyprogesterone and cortisol responses after ACTH stimulation in patients with non-hyperfunctioning and hyperfunctioning adrenal adenomas.

Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery.

To investigate the clinical significance of plasma dehydroepiandrosterone sulfate (DHEAS) measurements, 175 patients with histologically confirmed adrenal tumors, 10 cortisol-producing adenomas, 59 aldosterone-producing adenomas, 56 non-hyperfunctioning adenomas, 13 adrenocortical carcinomas, 13 adrenal cysts, and 24 adrenomedullary tumors were studied. Plasma DHEAS levels were expressed as percentage of the mean of sex- and age-matched groups of healthy, normal subjects (DHEAS %). We found that before adrenal surgery, DHEAS % values were significantly reduced in patients with cortisol-producing (mean, 15.2% of control; 95% confidence interval (CI), 9.4-24.7%), non-hyperfunctioning (28.4%; 22.4-36.0%) as well as aldosterone-producing adrenocortical adenomas (55.4%; 47.1-65.1%) compared with controls, while values were normal in patients with adrenal cysts and in those with adrenomedullary tumors. Plasma DHEAS % values exhibited a great variability in adrenocortical carcinomas (mean, 84.0%; 95% CI, 33.2-212.5%). Death from adrenocortical carcinoma was more frequent in patients with high plasma DHEAS % values compared with those with low DHEAS %. During long-term postoperative monitoring, we found that plasma DHEAS levels of patients with aldosterone-producing and non-hyperfunctioning adenomas returned to normal in the second and fourth postoperative year respectively. In patients with cortisol-producing adenomas, plasma DHEAS remained suppressed for as long as 8 years after the operation. These findings show that except in adrenocortical carcinomas and cysts, plasma DHEAS levels are significantly decreased in all groups of adrenocortical tumors, including non-hyperfunctioning and aldosterone-producing tumors. The extent of this decrease and the postoperative persistence of suppressed plasma DHEAS levels may be related to the glucocorticoid production of adrenocortical tumors.

[Multiple endocrine neoplasia]. / Multiplex endocrin neoplasiák.

The authors review present knowledge on multiple endocrine neoplasias types 1 and 2. They discuss in the light of recent literature data, the natural history, diagnosis, differential diagnosis and the optimal diagnostic approaches of these disorders. A short review on the therapeutic modalities draws attention to important differences between sporadic and inherited endocrine tumors. Finally, the authors emphasize recent developments about the genetic background and the importance of molecular biologic techniques, including family screening in the diagnosis of these disorders.